The multiple genetic markers (allotypes and idiotypes) of rabbit immunoglobulins and homogeneous antibodies will be used in studies to define the number and nature of genes encoding antibody variable regions. Segregation of VH allotypes with idiotypes of homogeneous antibodies have indicated linkage between these markers. Observations of unexpected combinations of these markers have suggested, however, that the genes encoding the binding site (idiotypes) are distinct from those encoding constant portions (allotypes) of the variable region. Further studies on idiotypes and group a allotypes will attempt to more completely define the genetic relationships between these putative V region genes. Recently described marker for the VL region will be used in experiments to obtain similar data for the antibody light chains. Studies on the subspecificities of the group a allotypes will be continued to determine whether these serologic variations within one allotypic determinant are caused by structural differences in the constant parts of the variable region or by modulation of identical determinants by differences in the hypervariable regions of idiotypically distinct molecules. The use of sensitive radioimmunoassays has shown the presence of group a allotypes not detected by quantitative typing nor anticipated from breeding data in the sera of about 50 percent of the rabbits tested. These latent allotypes were shown to occur in a transient and sporadic fashion. The molecules carrying latent allotypes will be fully characterized and studies will be carried out to determine whether the group b allotypes on the light chain behave in a similar nonallelic fashion. Sera containing latent allotypes will be examined for the presence of antibodies directed against these allotypes.